CAMP BINDING PROTEINS IN MAMMARY CANCER GROWTH CONTROL

CAMP 结合蛋白在乳腺癌生长控制中的作用

• 批准号: 3962974
• 负责人: Y S CHO-CHUNG
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3962974
• 关键词: affinity chromatography; breast neoplasms; cell free system; cell growth regulation; chemical binding; cyclic AMP; gel electrophoresis; hormone related neoplasm /cancer; human tissue; molecular oncology; molecular site; morphology; mouse mammary tumor virus; neoplasm /cancer therapy; neoplastic growth; prognosis; tissue /cell culture

Cyclic AMP (cAMP) in mammalian cells functions by binding to cAMP receptor protein, the regulatory subunit of cAMP-dependent protein kinase. The cAMP receptor protein has two different cAMP binding sites, and cAMP analogs that specifically bind to either one of the two binding sites are known as Site 1-selective (C-2 and C-8 analogs) and Site 2-selective (C-6 analogs), respectively. Further the Site 1- and Site 2-selective analogs in combination produce synergistic enhancement of the binding to cAMp receptor protein and protein kinase activation in vitro. Application of these in vitro findings to demonstrate cAMP analog-mediated response in vivo, in intact cells or tissues has been scarce. Moreover, virtually all past studies of cAMP-regulation of cell growth employed a few, early known, cAMP analogs which are weakly active for protein kinase and effective only at unphysiological high mM concentrations. The site-selective cAMP analogs which are many-fold more active for protein kinase have never been tested for their growth regulatory effect. We, therefore, investigated the effect of site-selective cAMP analogs on the growth and morphology of several breast and colon human cancer cell lines and the in vivo growth of rodent mammary tumors. The analog effect on the cell growth will be correlated with the response of cAMP receptor protein present in the cancer cells. The goal of this study is to elucidate the growth regulatory mechanism of cAMP analogs which can be extrapolated to the treatment of human cancer.

哺乳动物细胞中的环状AMP（CAMP）通过与cAMP受体结合而起作用 蛋白质，依赖CAMP的蛋白激酶的调节亚基。 营地 受体蛋白具有两个不同的cAMP结合位点和cAMP类似物 特异性结合到两个结合位点中的任何一个被称为 位点1选择性（C-2和C-8类似物）和位点2选择性（C-6类似物）， 分别。 此外，位点1和位点2选择性类似物 联合产生与cAMP受体结合的协同增强 蛋白质和蛋白激酶在体外活化。 这些体外发现的应用以证明CAMP模拟介导 体内反应，完整的细胞或组织中的反应很少。 而且， 几乎所有过去对细胞生长营地调节的研究 很少有早期已知的cAMP类似物，对于蛋白激酶而言弱活性 并且仅在非生理高的MM浓度下有效。 这 现场选择性camp类似物，蛋白质的活性更高 激酶从未对其生长调节作用进行测试。 因此，我们研究了现场选择性营地类似物对 几个乳腺和结肠人类癌细胞的生长和形态 线条和啮齿动物乳腺肿瘤的体内生长。 模拟效果 在细胞生长上将与CAMP受体的响应相关 蛋白质存在于癌细胞中。 这项研究的目的是 阐明可以是营地类似物的生长调节机制 推断到治疗人类癌症。